Low cell motility induced by hsp27 overexpression decreases osteolytic bone metastases of human breast cancer cells in vivo

The mechanisms controlling the formation of osteolytic bone metastases in p atients with breast cancer are still poorly understood. To explore the role of motility in the establishment of osteolytic bone metastases, we have us ed a model of bone metastasis in which MDA-MB-231 breast cancer cells exhib iting low (hsp27-transfectants) and high (control-transfectant) endogenous cell motility were compared. We found that MDA-MB-231 cells exhibiting low cell motility were less capable of establishing osteolytic lesions. The num ber and the area of the osteolytic lesions in mice inoculated with low moti lity cells were both significantly smaller. Histomorphometry of bone lesion s also demonstrated less tumor area in mice bearing hsp27 transfectants alt hough there was no difference in the osteoclast number per square millimete r of tumor-bone interface. These data suggest that cell motility may be an important mechanism in the metastatic cascade of breast cancer cells to the bone and that controlling cell motility may be a useful target to prevent the establishment of osteolytic bone metastases.